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Protecting the heart from cancer therapy

MAR 2010

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Battling cancer can have long-term effects on the heart.

Treating cancer isn't yet a precise science. Although doctors are getting better at targeting tumors, there's still no magic bullet that homes in on cancer cells and destroys them without risking collateral damage to other parts of the body. The outward signs of off-target destruction include classic side effects of chemotherapy and radiotherapy such as hair loss, nausea, and fatigue. But there can be silent inner damage, too, sometimes to the heart and arteries. These injuries can appear immediately during therapy; other times they don't surface for years.

"Important advances in our ability to fight cancer over the last few decades have translated into improved survival," says Dr. Erica L. Mayer, an oncologist at Harvard-affiliated Dana-Farber Cancer Institute. "But we are also learning that many of these lifesaving therapies have the potential to affect the heart and other parts of the body."

Once relegated to the back burner, the late effects of cancer care are gradually getting more attention. One turning point was the publication in 2005 of From Cancer Patient to Cancer Survivor: Lost in Transition. This influential report from the Institute of Medicine put a spotlight on the disjointed care often received by the 12 million-plus cancer survivors in the United States after their cancer treatment has ended.

The report has led to greater awareness by cancer specialists of the long-term physical, medical, and psychological needs of cancer survivors. One important item that's still in development: evidence-based strategies for the best way to monitor cancer survivors for late effects of cancer therapy.

A delicate balance

Most cancer-fighting techniques exploit cancer cells' tendency to grow quickly and divide rapidly. By interrupting the mechanics of cell division, chemotherapy and radiation therapy can stop cancer in its tracks. But since these therapies can't yet tell bad cells from good ones, they also affect healthy cells that grow and divide rapidly, like hair follicles and cells lining the stomach and intestines. Heart cells grow and divide very slowly. This makes them less sensitive to the effects of cancer therapy, but not impervious to it.

Fighting cancer is tricky business. The goal is to hit the cancer with effective doses of chemotherapy or radiation while minimizing side effects elsewhere in the body. Because these therapies can save lives, patients and doctors have traditionally tolerated long-term side effects. But as specialists develop more precise ways to deal with cancer, there is increasing emphasis on minimizing short- and long-term complications.

Chemotherapy

The drugs used to fight cancer extend life for millions of people and sometimes eradicate the disease completely. In doing so, they can also inadvertently harm the heart and arteries. Some chemotherapies can trigger immediate problems, such as blood vessel spasms or irregular heart rhythms, while others can set off slow changes that accelerate artery-clogging atherosclerosis or lead to heart failure.

Drugs often linked to heart damage include the anthracyclines and anthraquinolones — doxorubicin, daunorubicin, epirubicin, mitoxantrone, and others. They are used to treat a variety of cancers, including leukemia, lymphoma, and cancers of the breast, uterus, ovary, and lung. At high cumulative doses, these drugs can weaken the left ventricle, the heart's main pumping chamber, leading to heart failure. To prevent this from happening, doctors try to make sure that the lifetime dose of these medicines stays below the threshold for heart problems.

Trastuzumab (Herceptin) is an antibody treatment for one type of breast cancer. Treatment with trastuzumab has led to improvements in survival for women with this type of cancer. But it, too, can weaken the left ventricle. That's why women receiving trastuzumab should have their heart function monitored closely during treatment. Platinum-based agents like cisplatin, a mainstay for treating testicular cancer, can damage the inner lining of arteries, causing spasms that can lead to chest pain (angina) or Raynaud's disease.

The cardiac side effects of anthracyclines, trastuzumab, cisplatin, and other chemotherapy agents may be seen early, as treatment is under way. Temporarily stopping the drug, lowering the dose, or starting treatment with an ACE inhibitor or other heart-protecting medicine are ways to allow chemotherapy to continue. However, cardiac side effects can also emerge decades after treatment is completed. That's why it is important to be vigilant for new symptoms that could herald changes in heart function. Research to make chemotherapy less dangerous for the heart is under way.

Cardiac cancer — uncommon but possible

Heart cells grow and multiply at a glacial pace. Although this presents problems for healing after a heart attack, it makes the heart a relatively rare site for cancer. Yet cardiac cancer does occur. In the United States each year, several hundred people are diagnosed with tumors that originate in the heart (primary cardiac cancer). Many others develop cardiac tumors that have spread from elsewhere in the body (secondary or metastatic cancer). Up to three-quarters of all primary heart tumors are benign, meaning they don't grow in an unlimited, aggressive manner, don't invade surrounding tissues, and don't spread to other tissues (metastasize). Yet even benign tumors can interfere with the heart's vital function.

Primary cardiac tumors. Myxomas (mick-SOE-mahs) are the most common type of cardiac tumor. If detected and treated early, these benign tumors have little effect on lifespan. Most malignant primary cardiac cancers are soft-tissue tumors known as sarcomas. They tend to grow rapidly inside the heart and quickly spread to other tissues. This type of cancer is rare.

Metastatic cardiac tumors. Cancer cells that break away from tumors elsewhere in the body can grow in the heart. Almost any type of cancer can do this, but the most likely ones include lung, breast, skin (melanoma), stomach, and ovarian cancer. These secondary or metastatic tumors are far more common than primary cardiac tumors.

Effects on the heart

Any cardiac tumor can jeopardize the heart's ability to pump blood by preventing the heart from contracting, blocking blood flow into or out of the heart, taking up space inside one of its chambers, or interfering with the operation of a valve.

General, nonspecific symptoms of heart trouble are usually the first indications of a cardiac tumor. Unexplained shortness of breath, fainting, palpitations, chest pain, and fever are some of the most common symptoms. Swelling in the face or legs or distended veins in the neck are physical signs that sometimes herald a cardiac tumor. Still, the rarity of cardiac cancer coupled with symptoms that usually indicate more common forms of heart disease, such as heart failure or an infection of the heart, make pinning down the diagnosis difficult.

Treatment

Benign cardiac tumors are usually removed surgically. Survival following removal of a myxoma is often excellent. In a 48-year survey of surgery for cardiac tumors at the Mayo Clinic, people who had a myxoma removed lived as long as average Americans of the same age and gender.

The outlook for malignant primary or metastatic tumors is less favorable. Surgery and chemotherapy can extend survival, but don't always completely eradicate the cancer. Improving symptoms is often the focus of treatment.

Radiation therapy

Although heart tissue is relatively resistant to the effects of radiation, it is sometimes damaged by radiotherapy around the chest wall for breast, lung, or esophageal cancer or lymphoma. A side effect that appears early is pericarditis, inflammation of the protective sac around the heart (the pericardium). Radiation can also set off slower chains of events that lead to a range of cardiovascular problems, including valve trouble and rhythm problems. It can also cause premature stiffening and narrowing of the heart's arteries, which increases the chances of having a heart attack. Radiation-related damage to arteries can sometimes complicate later bypass surgery or angioplasty.

Post-radiation cardiovascular disease was much more common with older techniques used before the late 1980s. Newer radiation techniques, including 3-D planning with CT scans and tightly focused radiation beams, let doctors more precisely target tumors and shield the heart and other healthy tissues. Improvements in these technologies and the development of new ones will almost certainly further reduce the risk of radiation-related heart damage.

Hormone therapy

Some cancers are strongly influenced by hormones. Estrogen nurtures breast cancer; testosterone fuels prostate cancer. Drugs that block the production of these hormones, or cells' responses to them, can stifle cancer. They can also have some cardiovascular consequences.

Tamoxifen, an anti-estrogen used for treating breast cancer, somewhat increases the risk of potentially harmful blood clots (deep-vein thrombosis and pulmonary embolism). Men who take testosterone-blocking drugs for prostate cancer are slightly more likely to have heart attacks or develop diabetes or other cardiovascular problems compared with men who don't take these drugs.

Vigilant survivorship

As experts study the effects of cancer therapy on the heart and rest of the body, there are many things a cancer patient can do to be a healthy survivor.

"If you are undergoing treatment for cancer, the best thing you can do is pay attention to your body," advises Dr. Edward T.H. Yeh, who chairs the cardiology department at M.D. Anderson Cancer Center in Houston. If you are short of breath or develop chest pain or swelling in your legs, tell your oncologist so he or she can immediately refer you to a cardiologist. "It's all about collaboration, driven by the patient," says Dr. Yeh.

The same advice applies once you've finished treatment. Keeping on top of standard risk factors — like smoking, blood pressure, cholesterol, weight, physical activity, diet, and stress — can help prevent the appearance of heart disease. Being vigilant for signs of heart disease, and reporting them to your doctor, is equally important.

If life were completely fair, cancer survivors would be exempt from future health problems. Sadly, that isn't the case. Cancer survivors are prone to heart disease like everyone else, and perhaps a bit more so as a result of cancer therapy. Overall, cancer therapy saves lives, and doesn't cause long-term problems for most survivors. But since it is impossible to tell who will develop later complications, knowing that they can occur is important information to have.

To protect your hard-earned survivorship, pay attention to your heart and body and establish good communication with your cancer doctor, primary care doctor, and cardiologist.